Circ-0104631 promotes cell proliferation and invasion in colorectal cancer and predicts poor prognosis

摘要

OBJECTIVE: The aim of this study was to elucidate the effect of Circ-0104631 on the progression of colorectal cancer (CRC) and to demonstrate the underlying mechanism. Our research might provide new biological markers and molecular therapeutic targets for the diagnosis and therapy of CRC. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect Circ-0104631 expression in human colorectal cancer tissues and normal control tissues. To further explore the effect of Circ-0104631 on CRC in vitro, we first knocked down Circ-0104631 in colorectal cancer cells (SW480 and LoVo) by shRNA transfection. Subsequently, we detected its effect on cell proliferation and invasion by cell counting kit-8 (CCK-8) assay, colony formation assay and cell invasion assay, respectively. The regulation of Circ-0104631 on the expressions of phosphate and tension homology deleted on chromosome ten (PTEN)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway-related proteins was detected by Western blot. Besides, the regulatory mechanism of Circ-0104631 on the progression and metastasis of CRC was further verified by recovery experiments. RESULTS: QRT-PCR results showed that Circ-0104631 was highly expressed in tissues of patients with CRC when compared with that of normal control tissues. At the same time, we also found that the expression of Circ-010463 was significantly up-regulated in CRC tissues with high topography lymph node metastasis (TNM) stage and distant metastasis. Survival curve analysis indicated that high expression of Circ-010463 predicted poor prognosis of CRC patients. In vitro experiment demonstrated that inhibition of Circ-0104631 in SW480 and LoVo cells could markedly decrease cell growth and metastasis abilities. Meanwhile, Western blot results indicated that the protein expression of PTEN increased significantly, while p-Akt and p-mTOR decreased remarkably after knock-down of Circ-0104631 in CRC cells. Furthermore, recovery experiments illustrated that knockdown of PTEN in SW480 and LoVo cells partially attenuated the inhibitory effect of shRNA-Circ-0104631 on cell growth and metastasis. CONCLUSIONS: Circ-0104631 was highly expressed in CRC tissues. Furthermore, knockdown of Circ-0104631 could inhibit the growth and metastasis of CRC cells by regulating PTEN/Akt/mTOR signaling pathway.